COL11A1基因多态性与儿童大骨节病的关联分析

摘要

Objective To investigate the role of α1 of type collagen gene (COL11A1) in the pathogenesis of Kashin-Beck disease (KBD) in children .Methods From June to August in 2015 serum was collected and genomic DNA was obtained from 35 KBD cases and 84 healthy controls in Linyou County and Yongshou County of Shaanxi Province .Nine SNPs in COL11A1 were selected ,and genotypes were conducted using Sequenom assARRAY RS1000 .The frequencies of alleles and genotypes were compared between KBD group and control group .Three genetic models (dominant ,recessive and additive) were further evaluated using unconditional Logistic regression analysis .Results The allele frequency of rs2229783 was significantly different between two groups (χ2 = 8 .61 ,P < 0 .01) ,and the genotype frequencies of rs2229783 and rs1676486 were also significantly different between two groups (χ2 value was 21 .5 and 10 .4 ,respectively ,both P < 0 .05) .All the OR values of re2229783 in the models of dominant and additive were less than 1 (P < 0 .05) ,suggesting that the individuals with the mutant allele A had a reduced risk of KBD .OR value of rs1676486 in recessive mode was 3 .18 (P < 0 .05) ,which suggested that individual with genotype of AA in this locus has higher risk for KBD than individual with genotype GG and GA .Conclusion Polymorphism of COL11A1 gene is associated with the susceptibility of KBD in children .The allele A in 2229783 locus gene may be related to a decreased risk of KBD ,while genotype of AA in rs1135056 may be related to an increased risk of KBD .%目的 探讨COL11A1(Ⅺ 型胶原 α1链)基因多态性在儿童大骨节病(KBD)发病中的作用.方法 于2015年6月至8月在陕西省麟游县和永寿县大骨节病区收集35例KBD患儿(病例组)和84例健康儿童(对照组)全血并提取全血基因组DNA,应用Sequenom assARRAY RS1000分型技术对COL11A1上9个SNPs多态性位点进行基因分型,比较病例组与对照组等位基因和基因型的分布差异,进一步用非条件Logistics回归模型分析各等位基因在3种遗传模型(显性 、隐形和加权模型)下的效益.结果 位点rs2229783等位基因频率在两组儿童中有统计学差异(χ2=8.61,P<0.01),位点rs2229783和rs1676486的基因型频率分布在两组儿童中有统计学差异(χ2值分别为21.5、10.4,均P<0.05).位点re2229783在显性和加权遗传模型中的OR值小于1(P<0.05),提示该位点携带突变型等位基因A的个体患有KBD的风险降低.而位点rs1676486在隐性模式下(OR=3.18,P<0.05),提示该位点基因型为AA个体患KBD的风险高于基因型GG和GA的个体.结论 COL11A1基因多态性与儿童KBD的易患性有关,在2229783位点上个体携带等位基因A可能与KBD易患性的降低有关,在位点rs1135056上基因型为AA的个体KBD易患性增加.